This invention pertains to a liquid chromatography column cartridge, in particular, to a LC column cartridge comprising a memory component.
Molecules can be effectively separated by employing liquid chromatography (xe2x80x9cLCxe2x80x9d). A typical liquid chromatography system consists of a column and solvent which traverses the entire column. As the development of column packing material (also referred to as xe2x80x9cstationary phasexe2x80x9d) progressed, high pressure was required to pump solvent through the column leading to the development of high pressure liquid chromatography (HPLC).
High performance liquid chromatography systems typically consist of high pressure pumps, at least one solvent reservoir, a column capable of withstanding relatively high pressures, and a detector. Columns used in HPLC typically consist of packing material. In most instances this packing material comprises silica-based particles typically with functional groups (defining a column""s chemistry) attached to these silica-based particles. The packing of the column is a critical event in the construction of a specific column, for the integrity of the packed bed impacts the overall resolution capability of the column. As the bed becomes disrupted through any series of events, for example, sharp periodic fluctuations in column pressure, resolution will decrease. Maintaining the integrity of the packing bed is essential if the original efficiency capability of a particular column is to be preserved. Through continued usage, the column""s packed bed and the bonded phase deteriorate. The resolving power of the column is then lost. Detection and recordation of this loss of resolving power is very important.
Capillary liquid chromatography is a micro-version of traditional liquid chromatography. As is true for traditional liquid chromatography, the column used in capillary liquid chromatography is of critical import. These columns typically have low solvent consumption and require low volumes of sample for analysis. These conditions translate into a higher degree of unit mass detectability. Capillary liquid chromatography systems typically comprise a micro-pumping unit, a capillary column, a detector, and a data processing system. Capillary liquid chromatography columns are typically produced using such materials as fused silica, stainless steel, or polymeric compositions. The lumen of the capillary is packed with packing material containing separation material, such as bonded silica particles. Typically, the internal diameter of the capillary column is between 50 and 500 xcexcm.
Assessment of column quality is typically performed by running standard analytes through the column and comparing certain chromatographic parameters to a standard test run. Apart from performing a chromatographic run with known analytes, assessment of the column cannot be effectuated. Currently, columns themselves lack the ability to store their performance information which can be of great value. The performance record of a column is very important in environments where quality control is an issue, for example, in the pharmaceutical industry.
The present invention pertains to a LC column cartridge comprising a memory component integrally attached to it, for example, at the time of its manufacture, as well as a method for producing such a LC column cartridge with an integral memory. In one embodiment, the memory component is a semiconductor memory chip.
The amount of data stored will depend upon the memory capacity, and how the data is recovered will depend on whether or not a microcontroller is incorporated in the component itself. Components could be read only or read/write or be partitioned with a read only area for manufacturing information and a read/write area for usage data. The information stored could vary from the minimal amount of data required to identify the column and its quality control test performance in text format to a full quality control trace and usage history.
The instant invention encompasses at least two types of memory components. One memory component is specific for use on a specific HPLC system. This type of memory component is customized for use with a specific manufacturer""s HPLC system. In one illustrative embodiment, the memory component is read and writeable. The read only area comprises full column manufacturing and quality control test data. The writeable area can comprise a history of column usage, for example, number of injections, maximum used pressure, maximum used flowrate, pressure/flow profile, maximum temperature, serial number, as well as other features.
The other memory component can be employed in any HPLC system. In one illustrative embodiment, the memory component is a read only memory component and is supplied with a device to read the memory component and output the data in via, for example, a RS232 interface. The data in this illustrative embodiment can be limited to column manufacturing and quality control test data.
In another illustrative embodiment of the present invention, a method for constructing a liquid separation column smart cartridge is disclosed. An assembled cartridge is provided comprising all of the necessary elements for a smart separation HPLC column including a memory component. The memory component is then programmed at the manufacturing facility. The column is then packed with appropriate packing material based upon the specific use of the column. Following the packing of the column, the column undergoes testing for quality assurance at the manufacturing facility the results of which are then incorporated into the memory component. Following use by an end-user, the column can intermittently throughout its lifetime be examined for quality control issues, for example, in the process of validation of a particular chromatographic method. The column can be tested at a test site, for example, within an end-user""s facility, the results of which are then incorporated into the memory component.
This invention provides useful information as to the column""s performance which is critical in both Good Manufacturing Practice and Good Laboratory Practice settings. Damaged columns can be detected early, thereby saving on both frustration and useless data acquisition. The present invention provides a user-friendly environment which facilitates compliance with established criteria used in a validated protocol. Full traceability of the column throughout its lifetime is available to the end-user or any other interested party with appropriate access capabilities. This invention provides direct access to information concerning a particular column that has heretofore been unattainable to any end-user.
In accordance with one aspect of the liquid separation column smart cartridge technology disclosed here, an inlet orifice in the housing unit is in fluid communication with a first end of the liquid separation column within the housing and an outlet orifice in the housing unit is in fluid communication with a second end of the liquid separation column. As disclosed above, the liquid separation column provides a fluid flow path within the housing from the inlet orifice to the outlet orifice. First and second ferrule sub-assemblies are fitted to the first and second ends of the liquid separation column, respectively. More specifically, each of the ferrule sub-assemblies comprises a ferrule or end cap seated over the end of the column. The ferrule sub-assembly preferably comprises a compression ring securing the attachment to the liquid separation column. The ferrule sub-assemblies, further described below, each preferably provides a seating and sealing surface for its respective fluid flow port. Preferably the ferrule sub-assembly comprises a frit body providing the seating and sealing surface.
Preferably each of the ferrule sub-assemblies is secured to the housing in a fixed position, optionally being removably fixed, at its respective port. In this manner, the liquid separation column can be conveniently anchored to the housing, e.g., to a component of the housing which is assembled with one or more other housing components after the liquid separation column is attached, to construct the housing unit of the smart cartridge. More specifically, in accordance with certain illustrative embodiments, a surface of the ferrule sub-assembly at the inlet end of the liquid separation column is a substantially flat surface having a fluid opening for the inlet port and facing substantially outwardly from the housing to seat and seal conveniently against a corresponding surface of a fluid feed line or other fluid source feeding fluid to the liquid separation column smart cartridge for testing, analysis, etc. Similarly, a surface of the ferrule sub-assembly attached to the outlet end of the liquid separation column provides a substantially flat surface having a fluid opening for the outlet port and facing substantially outwardly from the housing to seat and seal conveniently against a corresponding surface of a fluid return or waste line or other fluid receiving device for accepting fluid from the liquid separation column smart cartridge after it has been tested, analyzed or subjected to other operation(s) by the liquid separation column within the housing. It should be recognized that the designation of a port of the housing unit as being an inlet port or an outlet port may in certain instances be arbitrary and merely a matter of convenience or choice, such as where the smart cartridge is usable in either direction, preferably then being side-to-side symmetrical so that it can be properly installed in either orientation. In another illustrative embodiment of the present invention, an outwardly extending connector is provided on a liquid column separation smart cartridge to enable insertion of the smart cartridge fluid ports into wells or receiving sockets of a manifold or mounting device or the like, for fluid connection and sealing.